Content+-+Drug+Development+Process

=Board Game Content Analysis=

**From A Compound to A Drug: The Drug Development Process** This game is a race through the drug development process. Players will compete to get their compound made into an FDA drug. Their drugs will each need to go through the various stages of development including, from research and development, non-clinical testing, clinical studies, and manufacturing. Players will learn about the overall processes that all drugs must go through to prove their safety and quality before they can be approved by the FDA for use in humans as well as a basic understanding of the key players and regulations that control each step in the process


 * ~ Content Type ||~ Content Elements ||~ Game Elements ||
 * === Facts ===

•   __ 1906 Federal Food and Drugs Act __ – prohibited interstate commerce in misbranded and adulterated drugs, drinks and food; law administered by FDA (result of meat packing industry conditions, dangerous patient medicines) •   __ 1938 Food, Drug and Cosmetic Act __ – law required that safety of drugs be demonstrated, authorized inspections, outlawed false claims, required a full list of ingredients and directions for safe use and gave FDA jurisdiction over companies (Elixir with antifreeze caused deaths of 107) •   New Drug Applications (NDAs) that requiring clinical data cost user’s fees of approximately $1,178,000 in 2008 •   FDA’s Performance Goals are to turnaround standard submission of new drug applications within 10 months (90%) and priority applications in 6 months (90%); Class 1 (resubmission) in 2 months (90%), priority (resubmission) in 2 month (90%) •   On average it takes 12 years for an experimental drug to go from a lab bench to be a manufactured drug •   __ Clinical Hold __ - FDA can place a clinical hold on Investigational New Drug Applications if they have concerns or issues regarding the investigational new drug •   Of the 5,000-10,000 drug compounds that ender Research and Development phase, only 5 make it to the clinical trial state •   Of the 5 compounds that enter clinical trial stage, only __one__ is approved for marketing •   __ Investigational New Drug application (IND) __ - application that must be submitted to the FDA for any compound that is new for intended use in humans and will be researched in non-clinical studies •   __ New Drug Application (NDA) __ – application to FDA to get drug approved for use in humans; includes administrative and prescribing information, document summaries, quality and non-clinical study reports •   Total NDA Received by the FDA in 2006 were 122 and a total of 80 were approved •   __ Adulterated __ – Addition or alteration of food or other products for humans that changes the original form and may cause harm •   __ Contamination __ - accidental introduction of "foreign" material which may seriously distort the results of experiments or the finished drug product •   __ Drug product containers and closures __ – containers and lids that are used to store and hold finished drug products •   New Drug Application approval can take 2-7 years to get approval •   __ Title 21 of the Code of Federal Regulations __ – set of FDA laws and regulations that govern the clinical, laboratory and manufacturing practices of drugs in the U.S. || Questions Cards: either general Fact, Chance or 3 stacks of Facts cards for each functional area - lab, clinical and manufacturing - will ask players to recall knowledge in each area or in general area || Spaces on board about each area of the board (historical facts)

Cards on board: different cards correlate to different parts of the board - lab, clinical and manufacturing || •   __ Specimen __ – an individual animal, part of an animal, plant, part of a plant, or microorganism used as a representative to study the properties of the whole population •   __ Compound __ - a combination of two or more elements •   __ Drug __ – chemically synthesized small molecules that are generally straightforward to manufacture and are regulated by the Federal Food, Drug and Cosmetic Act and governed by CDER in the FDA. They are considered articles other than food intended to affect the structure or any function of the body of man or other animals. Drugs use the marketing application NDA and are governed by Title 21 of the CFR. •   __ Biologics __ – biologically synthesized proteins that are generally thought to be more complex to manufacture in a consistent way. Governed by the Public Health Services Act and the CBER branch of the FDA. Biologics use the marketing application – BLA and must follow Title 42 of US CFR. They are considered any virus, serum, toxin, vaccine, allergenic product, etc. used to prevent or treat, cure a disease or condition in humans. •   __ GxP Regulations __ - generalization of quality guidelines, predominantly used in the pharmaceutical industry to describe good clinical, laboratory and manufacturing practices •   __ GLP regulations __ – laws that govern non-clinical studies and protect the integrity of lab data that supports product applications; •   __ GCP regulations __ – laws that govern clinical trials and protects participants health and safety during the studies •   __ GMP regulations __ – laws that govern the manufacturing of all drug products for humans. State the minimum standards for manufacturing, processing, packing and holding of drugs and finished pharmaceuticals •   __ Safety __ - drugs free from unexpected side effects •   __ Identity __ - label states exactly what the drug is    •    __ Strength __ – the drug delivers the correct dosage and potency over the products life •   __ Quality __ – the product meets pre-established standards; performs as claimed; is consistently produced to meet the same specifications every time •   __ Purity __ – the drug is free from physical, biological and chemical contamination •   __ FDA Guidance __ - documents that represent the FDA's current thinking on a particular subject, but are not binding legal requirements •   __ Informed consent __ : a legal condition in which a person gives written consent based on an understanding of the facts, implications and future consequences of the study. In order to give informed consent, the individual must have adequate reasoning faculties and be in possession of all relevant facts at the time consent is given •   __ Audit __ : Inspections or evaluations of a person, company, system, process, procedure or product, done internally or by the FDA to ensure the validity and reliability of the data and information •  __Clinical Study__: conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and approval is granted. Depending on the type of product and the stage of its development, investigators enroll healthy volunteers and/or patients into small pilot studies initially, followed by larger scale studies in patients that often compare the new product with the currently prescribed treatment. As positive safety and efficacy data are gathered, the number of patients is typically increased. Clinical trials can vary in size. •   __ Phase I stud __ y: study of healthy volunteers or targeted disease populations (patients) to develop initial safety, tolerability, pharmacokinetics and dosing, usually about 50-100 people •   __ Phase II study: __ study involving approximately 100-300 of the patient population; establishes short term measures of effectiveness, obtain additional safety information refine dosage •   __ Phase III study __ : involves larger patient population of about 1000-3000; establishes long-term effectiveness and safety •   __ Non-Clinical Study - t __ esting of safety of the drug before clinical trials can be done in humans. Determine a product's ultimate safety profile. Drugs may undergo pharmakonetics and toxicity testing through animal testing which help to estimate a safe starting dose of the drug for clinical trials in humans. Efficacy - the capacity to produce a desired size of an effect under ideal conditions •   __ Institutional Review Board __ – a committee that has been formally designated to approve, monitor, and review research and studies involving humans in order to protect the rights and welfare of the research subjects. The FDA has given IRBs the authority to approve, require modifications in (to secure approval), or disapprove research. An IRB performs critical oversight functions for research conducted on human subjects that are scientific, ethical , and regulatory. •   __ Adverse Event __ – any change in health or side-effect that occurs in a person who participates in a clinical trial while the patient is receiving the treatment study or within a pre-specified period of time after their treatment has been completed •   __ Standard Operating Procedure __ - written documentation that establishes standards which describe how to perform a task, process or procedure; must be strictly adhered to in GXP so that products and specimens are handled and produced consistently and accurately || Questions Cards: either general Fact, Chance or 3 stacks of Facts cards for each functional area - lab, clinical and manufacturing - will ask players to recall knowledge in each area or in general area || Cards on board: different cards correlate to different parts of the board - lab, clinical and manufacturing || •   The Food and Drug Administration (FDA) oversees the clinical, laboratory and manufacturing of drugs for humans in the U.S. They have jurisdiction over all U.S. pharmaceutical manufacturers and can audit, inspect and ensure companies follow laws and regulations. •   GXP Regulations govern the U.S. drug development process related to laboratory, clinical and manufacturing practices and must be followed at all times in all activities related to GxP. •   Companies that fail to follow laws and regulations face serious consequences from the FDA including facing fines and jail time, having holds on products, increasing audits and inspections, ordering studies be re-done or delayed and shutting down companies •   New products that are designed to treat human conditions or diseases are scrutinized by FDA's reviewers to ensure their safety, purity, quality, potency and strength before they can be approved and made available to consumers. •   All GxP personnel must be qualified to perform their jobs and have the education, experience and training to conduct their job - the FDA can issue a warning letter to the company to fix the situation if discovered which may cause delays in the approval process •   In non-clinical studies, animals of different species must be housed in separate rooms when necessary and animals of same species in different studies should be in separate spaces or have a differentiation process and identification to distinguish them from one another •   All companies must follow their approved protocols in non-clinical and clinical studies •   If there is a change to protocol, companies must have the new protocol reviewed and approved by the IRB before moving forward with the study •   Once an Investigational New Drug is submitted to the FDA, the company must wait 30 days before starting clinical trials (Phase I)    •    If an IND is placed on a “Clinical Hold,” the company must postpone the Phase 1 Clinical study until the hold is removed •   All clinical study participants must be informed of the relevant information about the investigational drug that will be studied and give their written consent documenting their agreement that they were informed about the studies details •   Clinical study participants may willingly drop out of a study at any time; if too many participants drop out; the study may need to be re-conducted •   If there are serious adverse events experienced during clinical studies, the study must be put on hold and the IRB must review the data to decide whether the study can continue or must be stopped •   All laboratory and manufacturing documentation on batch production must be kept 2 years past the batch expiration date for FDA inspection •   If something is not documented, it is considered not to have been done •   Standard Operating Procedures must be followed consistently and accurately by all employees to ensure the procedure is done the same way every time, producing the same results •   If a drug is contaminated, made incorrectly, or made using equipment that has not been calibrated or is out of service, the product could kill or harm a patient •   During manufacturing testing, drug batches must be destroyed if a sample is found to be adulterated, contaminated, impure or is out of specification •   Adequate safety data must be achieved in non-clinical studies to support starting dose and exposure during clinical trials •   The company is ultimately responsible for identifying specific safety issues and monitoring clinical trials •   Equipment must not alter or contaminate the product and must be tested regularly to ensure it is working accurately •   Logs must be kept on equipment use, cleaning, sanitizing, and calibration || Rules or laws that regulate the industry and control the drug development process || Rules of the game that control how a player can move and what phase he or she is in ||  ·  __ Writing Final Report in Non-clinical studies __ : Data is compiled, report written, study director reviews and signs-off, QA reviews and signs-off  ·  __ Writing and submitting protocols __ – submit to IRB, revise as necessary  ·  __ Setting up non-clinical study: __  Hire study director (overall technical conduct of study is within responsibility), QA Unit; facility suitable size (animal care and supply facility; lab operation areas specimen controls and data storage) – test and control articles must be recorded, stored properly, protocol is established, written procedures, monitoring and auditing system  ·  __ Clinical study procedures __ – must go through IRB, get informed consent, pick clinical investigators, select monitors; record data (paper or electronic), protocol, select investigators, monitors, train employees; review data from studies, maintain IND, inform FDA of safety information, monitor adverse events and report to IRB, maintain case histories; compile study data  ·  __ Manufacturing setup __ – obtain facility, ensure accurate location and size; obtain equipment, test; write SOPs; hire staff; ensure everything up to specification; order drug containers and components; ensure GMP regulations are followed; document  ·  __ Getting Informed consent __ – recruit subjects, inform of study design and effects, ensure subject voluntarily confirms willingness to participate in trial and is informed of all aspects of drug and potential effects; have subject document consent; sign and date  ·  __ Submission of IND __ – summary non-clinical studies; includes clinical trial protocol and final report; submit to FDA; FDA reviews; company receives acknowledgement letter; waits 30-days when review occurs; IND effective 30 days after receipt if no clinical hold  ·  __ Submission of NDA __ – submit to FDA, usually standard sometimes priority (products that meet unmet medical needs)  ·  __ Institutional Review Board’s procedures __ – review informed consent forms, monitor safety of subjects throughout studies, ensure protection of rights, safety and well being of subjects in clinical trials, review and approval of protocols, amendments, methods, documentation  ·  __ Quality Assurance procedures __  – check written procedures, review production and batch records, ensure errors are investigated and corrected; ensure written procedures are in place and being followed; approve and reject manufactured drugs; conduct internal audits || May be Question Cards asking players to perform a funtion, role a dice or give to another player - will determine when and how far the player can move in that area || spaces on the board within each area (lab, clinical or manufacturing) that will make players go through steps to leave the area ||  ·  __ Auditing __ - reveal if the company is following the laws and regulations and ensures that data and processes are truthful and accurate  ·  __ Records Management __ - is the practice of identifying, classifying, archiving, preserving, and destroying records, including the processes for capturing and maintaining evidence and data about business activities and transactions in the form of records  ·  __ Batch Production __ - All components are completed at a workstation before they move to the next one  ·  __ Drug discovery process __ – (takes ~1-3 years) screen compounds for specific biological activities, target drug design, natural product screening, identification of deficient proteins/peptides in certain disease  ·  __ Research and development __ – put together assessment, assemble IND, understand initial research data on candidate, generate data about and characteristics, do risk assessment, preliminary formulation screening (6-9 months)  ·  __ Preclinical Process __ – (9-15 months) prepare IND materials, get materials for clinical studies ready, develop Phase I formulation, determine method delivery, write IND, test and release clinical supplies for Phase I, and test formational for development supplies. <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  __ Conducting non-clinical studies __ – develop protocol, train staff, ensure accurate facilities; gather animals and monitor progress; ensure data is accurate; compile data <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  __ Conducting Clinical studies __ – (Phase 1, 2, 3, and 4; sometimes 2a and 2b or 3a and 3b instead (2-10 years);    •    Phase 1 test on small groups to determine safety and pharmacological data;    •    Phase 2 – once initial safety determined – trials test who suffer from condition may be divided into two phases IIA determine dosing and IIB to determine efficacy OR combine into one and monitor toxicity and efficacy together    •    Phase III randomized, controlled and larger population company efficacy of the new therapy with existing therapy; can be divide into 2 parts IIIA – pre-clinical, pharmacologic, efficacy, safety data, labeling, packaging production plans and IIIB – when IIIA is pending review and may demonstrate effeminacy for additional uses, supplemental safety data and support marketing claims •   Phase IV – post launch safety surveillance to detect long term effects <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  __ Manufacturing __ – establish plant, procedures, test and be ready for approval of drug <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  __ Post-Approval Company Procedures __ – monitor Adverse events, periodic safety updates to FDA, Phase 4 clinical trials to support safety; pediatrics studies; pregnancy registry; risk management || Will show steps in overall drug development process, show players the different processes that occur simaltaneously and in order to achieve the next level and move on in the game || Will appear as the map on the actual board. The board will be a race, but with 3 separate areas to designate the 3 processes of lab, clinical and manufacturing. There will also be Phases in the clinical studys that show up on the board to illustrate the complexity of each process. The players will use dice to roll through the path and move their drug along the process. || <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Equipment fails, malfunctions, not cleaned properly, contaminates product <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  FDA audits and inspects (surprise) <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Clinical Hold on IND application – must wait to start Phase I of Clinical Trials <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Adverse events experienced during clinical study – IRB must be contacted to decide if study should proceed <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Injured subject alleges inadequately informed of risks <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Subject accuses sponsor of continuing investigation with unreasonable significant risk <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Rouge employee doesn’t follow laws and regulations and is caught <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Employees aren’t properly trained to perform their jobs <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Drug product is contaminated or altered <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Data is reported inaccurately or dishonestly <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Computer error and data is not backed up properly <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Study participants drop out of the study <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Data is not reported accurately and tests must be redone <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Change in protocol – must go back through IRB approval process <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Study director quits in the middle of the study <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Funding <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> · Stock increases Approval process is longer than expected <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Study takes longer than expected <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Study results are not as expected <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Lack of funds to proceed <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Competition gets a similar drug approved by FDA first <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Initial study data may be insignificant <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Research and discovery results are not worth pursuing Better results than expected Clinical studies show amazing results <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  FDA turnaround time is not as expected <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Budget cuts <span style="FONT-SIZE: 10pt; FONT-FAMILY: Symbol; mso-fareast-font-family: Symbol; mso-bidi-font-family: Symbol"> ·  Staff turnover || Chance cards will show the random events that can delay or speed up the drug approval process || Chance spaces on the board and if a person lands on a space, they will have to draw a card which will change their fate or their opponents. || Context is the overall physical locations where each process occurs || Will show the overall drug development process from beginning to end as the phyical spaces that the drug travels through before reaching patients. || The board will be a linear model, but with 3 separate drawings of a lab, clinic and manufacturing plant to illustrate each phase of development. ||
 * ===Concepts===
 * ===Principles===
 * ===Procedures===
 * ===Processes===
 * ===Probabilities===
 * ===Context===
 * Pharmaceutical company
 * Lab for R&D
 * Board moves to Non-clinical study in lab with animals and Petri dishes
 * Clinical Study Phase, has different doctors clinics, office settings with patient files
 * Manufacturer phase moves into manufacturing plant with lab for testing, production line
 * Approval maybe marketing area
 * Different points of FDA intervenes
 * ===Vantage Points===
 * Adults in the pharmaceutical industry
 * General understanding of the drug development process
 * New hires with little knowledge about the entire drug development process
 * Different roles could include - management, CEO, manufacturer line workers; study directors; study monitor; quality assurance employee; regular employee; lab analyst; Regulatory Affairs; someone who works in lab, clinical or manufacturing area;
 * Patients
 * Sales Force who will be selling the product || The vantage point will be adults just hired at a pharmaceutical company with little knowledge about the entire drug development process - particularly the Sales Force who need a general understanding of what a drug goes through before it is marketed so they can understand how they fit into the overall process || Pawns shaped like pharmaceuticals, maybe different color pill shaped pawns to represent the different drugs. ||